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母体内暴露于十氯酮会影响组蛋白修饰，并激活脐带血中的 LINE-1。

In utero exposure to chlordecone affects histone modifications and activates LINE-1 in cord blood.

机构信息

University of Rennes, EHESP, Inserm, Institut de Recherche en Santé, Environnement et Travail (Irset)-UMR_S 1085, Rennes, France.

Institut de Génétique et Développement de Rennes, Epigenetics and Cancer Group, UMR 6290 CNRS, Université Rennes 1, Rennes Cedex, France.

出版信息

Life Sci Alliance. 2021 Apr 9;4(6). doi: 10.26508/lsa.202000944. Print 2021 Jun.

DOI:10.26508/lsa.202000944
PMID:33837044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8091598/
Abstract

Environmental factors can induce detrimental consequences into adulthood life. In this study, we examined the epigenetic effects induced by in utero chlordecone (CD) exposure on human male cord blood as well as in blood-derived Ke-37 cell line. Genome-wide analysis of histone H3K4me3 distribution revealed that genes related to chromosome segregation, chromatin organization, and cell cycle have altered occupancy in their promoters. The affected regions were enriched in ESR1, SP family, and IKZF1 binding motifs. We also observed a global reduction in H3K9me3, markedly in repeated sequences of the genome. Decrease in H3K9me3 after CD exposure correlates with decreased methylation in LINE-1 promoters and telomere length extension. These observations on human cord blood were assessed in the Ke-37 human cell line. H3K4me3 and the expression of genes related to immune response, DNA repair, and chromatin organization, which were affected in human cord blood were also altered in CD-exposed Ke-37 cells. Our data suggest that developmental exposure to CD leads to profound changes in histone modification patterns and affects the processes controlled by them in human cord blood.

摘要

环境因素可能会在成年后产生有害后果。在这项研究中，我们研究了宫内氯丹暴露对人类脐带血以及血液衍生的 Ke-37 细胞系的表观遗传效应。组蛋白 H3K4me3 分布的全基因组分析表明，与染色体分离、染色质组织和细胞周期相关的基因在其启动子中改变了占据。受影响的区域富含 ESR1、SP 家族和 IKZF1 结合基序。我们还观察到 H3K9me3 的整体减少，在基因组的重复序列中尤为明显。CD 暴露后 H3K9me3 的减少与 LINE-1 启动子的甲基化减少和端粒长度的延长相关。在 Ke-37 人类细胞系中评估了人类脐带血中的这些观察结果。在人类脐带血中受到影响的与免疫反应、DNA 修复和染色质组织相关的基因的 H3K4me3 和表达也在 CD 暴露的 Ke-37 细胞中发生了改变。我们的数据表明，发育过程中接触 CD 会导致组蛋白修饰模式发生深刻变化，并影响人类脐带血中受其控制的过程。

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